July 4th, 2011

Meta-Analysis: Increased CV Risk Associated with Varenicline (Chantix)

The anti-smoking drug varenicline (Chantix, Pfizer) is associated with an increased risk for serious adverse cardiovascular events, according to a new meta-analysis published in CMAJ.

In the meta-analysis, Sonal Singh and colleagues analyzed data from 14 double-blind randomized trials involving 8216 subjects. The rate of serious adverse cardiovascular events was 1.06% (52/4908) among varenicline recipients versus 0.82% (27/3308) among placebo recipients (odds ratio, 1.72; 95% CI, 1.09-2.71). The authors, led by Curt Furberg, estimated that the number needed to treat with varenicline for one additional person to successfully quit smoking was 10, whereas the number needed to cause one additional serious CV event was 28. The authors also noted that varenicline already has a black box warning about adverse neuropsychiatric symptoms.

In an associated commentary, J. Taylor Hays, who has conducted research on varenicline with funding from Pfizer, writes that “the small absolute risk of cardiovascular events associated with varenicline treatment is outweighed by the enormous benefit for reducing cardiovascular morbidity and mortality that can be achieved with successful smoking abstinence.”

The CMAJ paper follows a statement issued by the FDA on June 16, which warned that the drug might increase the risk for cardiovascular events in people who already have cardiovascular disease. “This would have raised a red flag for us if the flag hadn’t already been flying,” said the FDA’s Celia Winchell, in an interview with the New York Times.

The Times also quoted Furberg, who has served as an expert witness in cases against Pfizer: “We have known for many years that Chantix is one of the most harmful prescription drugs on the U.S. market, based on the number of serious adverse effects reported to the FDA. It causes loss of consciousness, visual disturbances, suicides, violence, depression and worsening of diabetes. To this list we now can add serious cardiovascular events.”

In a press release, Pfizer said that the meta-analysis was unreliable and that “the currently available safety data on Chantix… do not support an increased cardiovascular risk associated with Chantix.”

5 Responses to “Meta-Analysis: Increased CV Risk Associated with Varenicline (Chantix)”

  1. What continues to bother me is that the companies (Pfizer in this case) does not share its data so that investigators can conduct well done safety analyses on all patient-level data, published and unpublished, held by the company. Investigators are conducting these studies with one hand tied behind their backs. In this case they can only make inferences based on summary published data – and I am sure that does not tell the whole story. In the public interest the companies should be sharing their data.

  2. Leon Hyman, Ms M.D. says:

    Who to believe, Pfizer who makes money off the product, or a Dr who makes money testifying against Pfizer in law suits. Pfizer should listen to Dr. Krumholz and release all is data.

    Competing interests pertaining specifically to this post, comment, or both:

  3. Jean-Pierre Usdin, MD says:

    This is another stone in the story of Varenicline and above all in the field of quit-smoking medications.
    Personnally I prescribed Varenicline shortly after it comes on the french market.
    However many patients (specially female nurses) reported nightmares and sleeping uncomfort which conducted to the discontinuation of the treatment (and unfortunatly back to smoke…)
    At the present time, to my knowledge, only nicotin substitutes have no cardio vascular and general harmful (but side)effects. Now I use only these products.
    However separate the side effects of the medication from symptoms of cessation is difficult to admit by the smoker.

    Competing interests pertaining specifically to this post, comment, or both:
    no conflicts.

  4. Guy De Gent, MD says:

    I have not figured out how they got to these numbers. As a matter of fact, 14 trials were analyzed and all but one excluded patients with underlying CAD. I have not been able to get a hold of the full original papers. Based on the quoted numbers the odds ratio is 1.301 for a 99% CI that is not significant. RR increase is 29.8% , also not significant at the 99% CI interval (-29.3 to 183.4), it is also not significant at the 95% confidence interval .The NNH would be 412. Probably more important is to see the risk in patients with CAD. Nevertheless, there is a cautionary tale here and I have not prescribed Chantix yet, mainly because of lack of long term data on patient outcome. Short term, 1 in 10 stops smoking but what does that mean after one year (including relapses). There is no data how this translates in improvement in CV morbidity and mortality. We think it should, but there are no data. Chantix does have a lot of nasty side effects including visual disturbances, violence, nightmares, depression and worsening diabetes: therefore the benefit in CV morbidity /mortality is by no means clear. Chantix is better than placebo , but no better than nicotine patches. Regardless the NNH, for me the choice is easy, particularly with my distrust in the integrity of data generated by drug companies when it involves “blockbuster “ drugs (i.e. hiding for years the increased risk of suicide of SSRI’s in adolescents, creating a market for social phobias, and we can go on and on…). In the absence of the above data, there is as of yet no clear reason to subscribe Chantix. Unfortunately we tend to jump on the band wagon of new drugs far to quickly.

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  5. Jose Maria Julian, Physician says:

    I´ve used Champix since at this moment is the drug recommended by the Spanish Society of Cardiology to quit smoking. I have two patient´s so far on Champix, both women with history of high blood pressure and carotid atheroma plaques, no history of cardiovascular events, and severe difficulty on quiting smoking.

    So far the treatment is helping a lot. They haven´t described any secondary effects from the drug. I check on them frequently, every 15 days during all the treatment to make sure everything is fine and no mood disorder comes out.

    For my patients is working. TV´s has rised concerned about the drug and is difficult to begin a treatment when the patients directly tell you the drug was on TV the day before, and they said it kills. Maybe I´m safer smoking.

    Competing interests pertaining specifically to this post, comment, or both: